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5 Biomarkers for Overcoming Colorectal Cancer Drug Resistance Identified
< Professor Kwang-Hyun Cho's Team > KAIST researchers have identified five biomarkers that will help them address resistance to cancer-targeting therapeutics. This new treatment strategy will bring us one step closer to precision medicine for patients who showed resistance. Colorectal cancer is one of the most common types of cancer worldwide. The number of patients has surpassed 1 million, and its five-year survival rate significantly drops to about 20 percent when metastasized. In Korea, the surge of colorectal cancer has been the highest in the last 10 years due to increasing Westernized dietary patterns and obesity. It is expected that the number and mortality rates of colorectal cancer patients will increase sharply as the nation is rapidly facing an increase in its aging population. Recently, anticancer agents targeting only specific molecules of colon cancer cells have been developed. Unlike conventional anticancer medications, these selectively treat only specific target factors, so they can significantly reduce some of the side-effects of anticancer therapy while enhancing drug efficacy. Cetuximab is the most well-known FDA approved anticancer medication. It is a biomarker that predicts drug reactivity and utilizes the presence of the ‘KRAS’ gene mutation. Cetuximab is prescribed to patients who don’t carry the KRAS gene mutation. However, even in patients without the KRAS gene mutation, the response rate of Cetuximab is only about fifty percent, and there is also resistance to drugs after targeted chemotherapy. Compared with conventional chemotherapy alone, the life expectancy only lasts five months on average. In research featured in the FEBS Journal as the cover paper for the April 7 edition, the KAIST research team led by Professor Kwang-Hyun Cho at the Department of Bio and Brain Engineering presented five additional biomarkers that could increase Cetuximab responsiveness using systems biology approach that combines genomic data analysis, mathematical modeling, and cell experiments. The experimental inhibition of newly discovered biomarkers DUSP4, ETV5, GNB5, NT5E, and PHLDA1 in colorectal cancer cells has been shown to overcome Cetuximab resistance in KRAS-normal genes. The research team confirmed that when suppressing GNB5, one of the new biomarkers, it was shown to overcome resistance to Cetuximab regardless of having a mutation in the KRAS gene. Professor Cho said, “There has not been an example of colorectal cancer treatment involving regulation of the GNB5 gene.” He continued, “Identifying the principle of drug resistance in cancer cells through systems biology and discovering new biomarkers that could be a new molecular target to overcome drug resistance suggest real potential to actualize precision medicine.” This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (2017R1A2A1A17069642 and 2015M3A9A7067220). Image 1. The cover of FEBS Journal for April 2019
Mobile Software Platform Research Center Recognized by the MSIP
The Mobile Software Platform Research Center (MSPRC) at KAIST received an award from the Minister of Science, ICT and Future Planning of Korea on November 29, 2016, at Coex in Seoul. The award was presented at the Conference of Software R&D Annual Report 2016 hosted by the Ministry of Science, ICT and Future Planning (MISP) and the Institute for Information and Communications Technology Promotion (IITP). The research center developed user experience (UX)-oriented mobile software platforms that support the invention of next-generation UX service technologies. The center has filed 37 patents and registered 15 technologies. Its researchers received ten Best Paper Awards and published a total of 133 papers in Korean and international journals. Research teams at MSPRC expect that their software platforms will offer training programs for software engineers and new UX services. They also said that their extensive event processing platforms would reduce energy consumption on mobile devices. Professor Seungryoul Maeng of the School of Computing, the Director of MSPRC, said, “This is a great honor for us. I am greatly thankful for the teamwork of participating departments--Computer Science, Industrial Design, and Industrial and Systems Engineering. We will continue to introduce our research outcomes and to work towards commercializing these results.” Members of the Mobile Software Platform Research Center, KAIST
Professor Kun-pyo Lee Appointed Honorary Fellow of the Design Research Society
Founded in the United Kingdom (UK) in 1966, the Design Research Society is an international academic organization that promotes excellence in design and supports the interests of the design research community. Professor Kun-pyo Lee of the Industrial Design Department at KAIST received his honorary fellowship from the Society at its 50th international conference held from June 27, 2016 to July 3, 2016 in Brighton, UK. The Society recognized Professor Lee’s academic achievements and his contribution to the advancement of design research nationally and globally. To date, only eight researchers have received honorary fellowships from the Society, and he is the first Asian to become an honorary fellow. Professor Lee has worked at KAIST for more than 30 years as a professor in industrial engineering and served on various important positions such as the president of the Korean Society of Design Science, the president of the International Association of Societies of Design Research, an executive vice president of the Corporate Design Center at LG Electronics, and an advisory board member for Human-centered Design Network in Japan and UXnet in the United States. By introducing the concept of user experience (UX) in Korea for the first time, he developed this field while focusing on user-centered designs to optimize interactive digital products as well as interaction design to create mental and physical interfaces between people and interactive digital products, services, and systems. Professor Lee said, “I am pleased to become an honorary fellow of the Design Research Society. For quiet some time, industrial design remained in the domain of practical studies, lacking the kind of support needed to grow as an independent academic and research discipline, but this has changed rapidly in recent years. I will continue to remain actively involved in the development of industrial design engineering in Korea and the world.”
Bioengineers develop a new strategy for accurate prediction of cellular metabolic fluxes
A team of pioneering South Korean scientists has developed a new strategy for accurately predicting cellular metabolic fluxes under various genotypic and environmental conditions. This groundbreaking research is published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) on August 2, 2010. To understand cellular metabolism and predict its metabolic capability at systems-level, systems biological analysis by modeling and simulation of metabolic network plays an important role. The team from the Korea Advanced Institute of Science and Technology (KAIST), led by Distinguished Professor Sang Yup Lee, focused their research on the development of a new strategy for more accurate prediction of cellular metabolism. “For strain improvement, biologists have made every effort to understand the global picture of biological systems and investigate the changes of all metabolic fluxes of the system under changing genotypic and environmental conditions,” said Lee. The accumulation of omics data, including genome, transcriptome, proteome, metabolome, and fluxome, provides an opportunity to understand the cellular physiology and metabolic characteristics at systems-level. With the availability of the fully annotated genome sequence, the genome-scale in silico (means “performed on computer or via computer simulation.”) metabolic models for a number of organisms have been successfully developed to improve our understanding on these biological systems. With these advances, the development of new simulation methods to analyze and integrate systematically large amounts of biological data and predict cellular metabolic capability for systems biological analysis is important. Information used to reconstruct the genome-scale in silico cell is not yet complete, which can make the simulation results different from the physiological performances of the real cell. Thus, additional information and procedures, such as providing additional constraints (constraint: a term to exclude incorrect metabolic fluxes by restricting the solution space of in silico cell) to the model, are often incorporated to improve the accuracy of the in silico cell. By employing information generated from the genome sequence and annotation, the KAIST team developed a new set of constraints, called Grouping Reaction (GR) constraints, to accurately predict metabolic fluxes. Based on the genomic information, functionally related reactions were organized into different groups. These groups were considered for the generation of GR constraints, as condition- and objective function- independent constraints. Since the method developed in this study does not require complex information but only the genome sequence and annotation, this strategy can be applied to any organism with a completely annotated genome sequence. “As we become increasingly concerned with environmental problems and the limits of fossil resources, bio-based production of chemicals from renewable biomass has been receiving great attention. Systems biological analysis by modeling and simulation of biological systems, to understand cellular metabolism and identify the targets for the strain improvement, has provided a new paradigm for developing successful bioprocesses,” concluded Lee. This new strategy for predicting cellular metabolism is expected to contribute to more accurate determination of cellular metabolic characteristics, and consequently to the development of metabolic engineering strategies for the efficient production of important industrial products and identification of new drug targets in pathogens.”
Ju-pyeong Lee won the Best Paper Award from IEEE RTAS
Ju-pyeong Lee, doctoral student of the Dept. of Electrical Engineering of KAIST, received the Best Paper Award from the 11th Institute of Electrical and Electronics Engineers Real-Time and Embedded Technology and Applications Symposium (IEEE RTAS) sponsored by IEEE TC on Real Time System and supported from the U.S. National Science Foundation. He is in the Computer Engineering laboratory, and won the honor by his research of technique of Delayed Locking Technique for Improving Real-Time Performance of Embedded Linux by Prediction of Timer Interrupt. His paper was selected to be the best because of its practicality. His research purposed the technique that can dramatically improve real time problem, which was indicated to be the big problem of Linux. Moreover, he presented the way to easily materialize this technique in the practical system. Best Paper Award is the prize awarded by IEEE Computer Society in the recognition of outstanding achievement in the field of real time system and embedded technology. IEEE RTAS is a symposium held annually by IEEE. In this year, the 11th symposium was held from March 7 to March 10, for four days, in San Francisco, United States. The purpose of this year symposium was to seek papers describing significant contributions both to state of the art and state of the practice in the broad field of embedded and open real-time computing, control, and communication. Therefore, it especially focused on online real-time and embedded applications ranging from industrial embedded applications such as aeronautics and automotive systems to open multimedia, telecommunication and mobile computing systems. Approximately 200 related erudite from almost 20 countries including United States, England, France, Germany, Italy, and Sweden participated in this symposium. Total number of papers submitted to IEEE RTAS was 158, while only 53 of them were selected. by Hye-jung Won / Staff ReporterApril, 2005 / The KAIST Herald
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